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Background This meta-analysis aimed to test the hypothesis that the HER2-positive metastatic breast cancer (mBC) patients treated with anti-HER2 antibodies in trial intervention arms have a greater prolongation of overall survival (OS) than of progression-free survival (PFS) and this extra-prolongation of median survival time in OS relates specifically to the anti-HER2 antibody. Methods The NCBI/Pubmed and Cochrane databases were searched systematically for HER2-positive or mBC trials published in English during January 1999–November 2017. Treatment arms with shorter PFS were considered as the “control” arm, whereas those with longer PFS as the “test” arm. The between-treatment drug differences were grouped into nine categories. Groups with or without anti-HER2 antibodies were pooled respectively for comparisons. The interrelationships between PFS and OS hazard ratios (HRs) and median survival time differences were investigated by conducting fixed-effects and mixed-effects linear meta-regression analyses. Results Twenty-eight trials (10,928 patients) from 438 articles were collected, and four with missing data were excluded in meta-regression analysis. Overall median PFS (HR = 0.73, 95% CI: 0.68–0.78) and median OS (HR = 0.82, 95% CI: 0.77–0.87) weakly favored the longer PFS arm with a weak correlation between the PFS and OS HRs. However, the between-treatment drug difference was anti-HER2 antibody, the absolute increment in median OS time was double that of median PFS time (p, Highlights • Our study dissected the overall survival benefit over progression-free survival in HER-2 positive metastatic breast cancer treated with anti-HER2 antibody by meta-analysis. • Use of anti-HER2 antibodies, but not other anticancer drugs, to treat HER2-positive metastatic breast cancer independently predicted the OS compared with PFS. • The design of future clinical trials should consider anti-HER2 antibodies carefully in the treatment armamentarium for HER2-positive metastatic breast cancer.

SummaryBackgroundThis study aimed to evaluate the prediction capabilities of clinical laboratory biomarkers to the prognosis of COVID-19 patients.MethodsObservational studies reporting at least 30 cases of COVID-19 describing disease severity or mortality were included. Meta-data of demographics, clinical symptoms, vital signs, comorbidities, and 14 clinical laboratory biomarkers on initial hospital presentation were extracted. Taking the outcome group as the analysis unit, meta-regression analysis with the generalized estimating equations (GEE) method for clustered data was performed sequentially. The unadjusted effect of each potential predictor of the three binary outcome variables (i.e., severe vs. non-severe, critically severe vs. non-critically severe, and dead vs. alive) was examined one by one by fitting three series of simple GEE logistic regression models due to missing data. The worst one was dropped one at a time. Then, a final multiple GEE logistic regression model for each of the three outcome variables was obtained.FindingsMeta-data was extracted from 76 articles, reporting a total of 26,627 cases of COVID-19. Patients were recruited across 16 countries. The number of studies (patients) included in the final models of the analysis for severity, critical severity, and mortality was 38 studies (9,764 patients), 21 studies (4,792 patients), and 24 studies (14,825 patients), respectively. After adjusting for the effect of age, lymphocyte count mean or median ≤ 1.03 (estimated hazard ratio [HR] = 46.2594, p < 0.0001), smaller lymphocyte count mean or median (HR < 0.0001, p = 0.0028), and lymphocyte count mean or median ≤ 0.8714 (HR = 17.3756, p = 0.0079) were the strongest predictor of severity, critical severity, and mortality, respectively.InterpretationLymphocyte count should be closely watched for COVID-19 patients in clinical practice.

Background/Purpose: Even with the increasing recognition of primary aldosteronism (PA) as a cause of refractory hypertension and an issue of public health, the consensus of its optimal surgical or medical treatment in Taiwan has not been reached. Our objective was to develop a clinical practice guideline that is feasible for real-world management of PA patients in Taiwan. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force recognized the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics and constraints into PA management. Results: In patients with lateralized PA, including aldosterone producing adenoma (APA), laparoscopic adrenalectomy is the ‘gold standard’ of treatment. Mini-laparoscopic and laparoendoscopic single-site approaches are feasible only in highly experienced surgeons. Patients with bilateral adrenal hyperplasia or those not suitable for surgery should be treated by mineralocorticoid receptor antagonists. The outcome data of PA patient management from the literature, especially from PA patients in Taiwan, are reviewed. Mental health screening is helpful in early detection and management of psychopathology among PA patients. Conclusion: We hope this consensus will provide a guideline to help medical professionals to manage PA patients in Taiwan to achieve a better quality of care. Keywords: Primary aldosteronism, Guideline, TAIPAI

Background: This study aimed to evaluate the prediction capabilities of clinical laboratory biomarkers to the prognosis of COVID-19 patients. Methods: Observational studies reporting at least 30 cases of COVID-19 describing disease severity or mortality were included. Meta-data of demographics, clinical symptoms, vital signs, comorbidities, and 14 clinical laboratory biomarkers on initial hospital presentation were extracted. Taking the outcome group as the analysis unit, meta-regression analysis with the generalized estimating equations (GEE) method for clustered data was performed sequentially. The unadjusted effect of each potential predictor of the three binary outcome variables (i.e., severe vs. non-severe, critically severe vs. non-critically severe, and dead vs. alive) was examined one by one by fitting three series of simple GEE logistic regression models due to missing data. The worst one was dropped one at a time. Then, a final multiple GEE logistic regression model for each of the three outcome variables was obtained. Findings: Meta-data was extracted from 76 articles, reporting a total of 26,627 cases of COVID-19. Patients were recruited across 16 countries. The number of studies (patients) included in the final models of the analysis for severity, critical severity, and mortality was 38 studies (9,764 patients), 21 studies (4,792 patients), and 24 studies (14,825 patients), respectively. After adjusting for the effect of age, lymphocyte count mean or median ≤ 1.03 (estimated hazard ratio [HR] = 46.2594, p < 0.0001), smaller lymphocyte count mean or median (HR < 0.0001, p = 0.0028), and lymphocyte count mean or median ≤ 0.8714 (HR = 17.3756, p = 0.0079) were the strongest predictor of severity, critical severity, and mortality, respectively. Interpretation: Lymphocyte count should be closely watched for COVID-19 patients in clinical practice. Funding: None to declare. Declaration of Interest: None to declare.

The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.

Background Patients with childhood cancer are at increased risk for the development of second cancers. Methods A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed. Results We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer. Conclusion Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.

BackgroundHow could we anticipate the progression of the ongoing epidemic of the coronavirus disease 2019 (COVID-19) in China? As a measure of transmissibility, we aimed to estimate concurrently the time-varying reproduction number over time during the COVID-19 epidemic in China.MethodsWe extracted the epidemic data from the “Tracking the Epidemic” website of the Chinese Center for Disease Control and Prevention for the duration of January 19, 2020 and March 14, 2020. Then, we specified two plausible distributions of serial interval to apply the novel estimation method implemented in the incidence and EpiEstim packages to the data of daily new confirmed cases for robustly estimating the time-varying reproduction number in the R software.ResultsThe epidemic curve of daily new confirmed cases in China peaked around February 4–6, 2020, and then declined gradually, except the very high peak on February 12, 2020 owing to the added clinically diagnosed cases of the Hubei Province. Under two specified plausible scenarios for the distribution of serial interval, both curves of the estimated time-varying reproduction numbers fell below 1.0 around February 17–18, 2020. Finally, the COVID-19 epidemic in China abated around March 7–8, 2020, indicating that the prompt and aggressive control measures of China were effective.ConclusionSeeing the estimated time-varying reproduction number going downhill speedily was more informative than looking for the drops in the daily number of new confirmed cases during an ongoing epidemic of infectious disease. We urged public health authorities and scientists to estimate time-varying reproduction numbers routinely during an epidemic of infectious diseases and to report them daily to the public until the end of the epidemic.

Background Primary aldosteronism ( PA ) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new‐onset atrial fibrillation ( NOAF ) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF , and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow‐up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, P =0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; P =0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF . However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy.

Background Primary aldosteronism is the most common cause of secondary hypertension and is associated with left ventricular hypertrophy. However, whether aldosterone excess is responsible for left ventricular (LV) diastolic dysfunction is unknown. Methods and Results We prospectively enrolled 129 patients with aldosterone‐producing adenoma and 120 patients with essential hypertension, and analyzed their clinical, biochemical, and echocardiographic data, including tissue Doppler images. The patients with aldosterone‐producing adenoma were reevaluated 1 year after adrenalectomy. After propensity score matching, there were 105 patients in each group. The patients with aldosterone‐producing adenoma had worse diastolic function than the patients with essential hypertension, as reflected by lower e′ ( P P =0.003). Multivariate analysis showed that LV diastolic function was significantly correlated with age ( P P P =0.002), systolic blood pressure ( P =0.004), creatinine ( P =0.008), and log‐transformed aldosterone‐renin ratio ( P =0.003). After adrenalectomy, the patients with aldosterone‐producing adenoma had significant improvements in LV diastolic function as reflected by an increase in e′ ( P =0.003) and decrease in E/e′ ( P =0.002). The change in E/e′ was independently correlated with baseline E/e′ ( P P =0.006). Conclusions The patients with primary aldosteronism had worse LV diastolic function than the patients with essential hypertension after propensity score matching, and this could be reversed after adrenalectomy, suggesting that aldosterone excess may induce LV diastolic dysfunction.

AIM Increased oxidative stress significantly modifies the outcome of patients with diabetes mellitus (DM) and end-stage renal disease (ESRD), and is counteracted by antioxidative capacity. We aimed to investigate whether antioxidant single nucleotide polymorphisms (SNPs) influence the outcome of ESRD individuals and the influences exerted by DM, which has not been tested before. METHODS We prospectively enrolled multi-centre ESRD patients of Han Chinese origin between 2002 and 2003, recording their antioxidant (superoxide dismutase [SOD2], glutathione peroxidase [GPX1]) and peroxisome proliferator activated receptor-γ (PPAR-γ) genotyping results, and stratified based on DM. They were followed up until 2008, with risk factors for mortality analyzed by Cox proportional hazard regression. RESULTS We discovered that diabetic ESRD carriers of CC genotype of SOD2 exon 2 had an increased risk of mortality compared to non-diabetic ones with other genotypes (hazard ratio [HR] 4.04, P = 0.04), while GPX1 SNPs had no influence. Interactions between SOD2 and PPAR-γ SNPs regarding the mortality influence were also detected (for SOD2 CC genotype x PPAR-γ exon 6 CT genotype, HR 3.19, P = 0.008), suggesting the importance of considering a combination panel of SNPs on patient survival. CONCLUSION This might be the largest study focusing on the relationship between antioxidant SNPs and the outcomes of diabetic ESRD patients of Han Chinese origin. More studies are needed to validate our findings.

Current guidelines recommend harvesting ≥3 sentinel nodes if sentinel lymph node biopsy (SLNB) alone is considered after neoadjuvant therapy (NAT) for initially node-positive (cN+) breast cancer. We attempted to investigate factors predicting one or two sentinel lymph nodes harvested to be accepted for SLNB alone after NAT in initially cN + patients.Overall, 157 patients who received NAT (clinically T1-3/N1-2/M0) and underwent SLNB were identified from a prospectively maintained database. Significant factors were identified using a multiple logistic regression model.The overall SLN identification rate was 83.4%. Failed SLN identification was associated with a 2-day protocol using a single tracer (odds ratio: 0.331 [95% confidence interval {CI}: 0.132-0.830], p = 0.018), age52 years (0.345 [0.131-0.913], p = 0.032), and lobular histology (0.156 [0.026-0.944], p = 0.043). The overall false-negative SLNB rate was 14.7%. Its increased risk was associated with radioactivity count530 for any SLN during SLNB (96.4 [4.00-2320], p = 0.005), age ≥57 years (34.2 [1.92-610], p = 0.016), and taxane use (105 [1.02-10700], p = 0.049); its decreased risk was associated with more harvested SLNs (0.191 [0.054-0.669], p = 0.01) and dual tracers (0.101 [0.012-0.843], p = 0.034). A predictive model using these factors achieved an area under the curve of 0.935 (95% CI: 0.878-0.991).When taxane was administered during NAT, the false-negative rate was predicted at5% for patients aged57 years, if 1-2 SLNs were harvested using dual tracers, and when the count of every SLN was lower than 530 after NAT in cN + breast cancer.

Background/Purpose: Even though the increasing clinical recognition of primary aldosteronism (PA) as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA. Results: When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR) should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS) or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation. Conclusion: With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA. Index words: Primary aldosteronism, Guideline, TAIPAI, TSA

Aim Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. Methods The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. Conclusion The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

Objective International institutes have developed their own clinical performance indicators for ambulance services. It is unknown whether these process measures are related to survival of patients after out-of-hospital cardiac arrest (OHCA). We aimed to determine whether Emergency Medical Service (EMS)-related ambulance team process measures correlate with patient survival. Methods Four years of observational data were collected from an urban EMS OHCA registry. The two process measures were achieving an EMS response time ≤4 min and prehospital ROSC (return of spontaneous circulation). The outcome measure was survival to discharge. We used the GLMM (generalised linear mixed model) with stepwise selection to examine this process-outcome link at the patient and EMS team levels, respectively. Results We analyzed 3856 OHCA patients distributed across forty-three EMS ambulance teams. Survival to discharge was observed in 193 (5%) patients. The two EMS team process measures were positively associated with an improvement in survival at the patient level after case-mix adjustment. However, they were not associated with improvement in the risk-adjusted survival rate. Conclusions The EMS team-level process measures proposed by international institutes may not predict the risk-adjusted survival rate. Using these measures to motivate EMS teams to improve their quality performance would be questionable. Increased efforts should be devoted to constructing more pivotal EMS team-level process measures that are tightly linked to survival.

BACKGROUND AND AIMS Fibroblast growth factor 19 (FGF19) and fibroblast growth factor receptor 4 (FGFR4) signalling play critical roles in hepatocarcinogenesis. This study explored the potential of FGF19- and FGFR4-related biomarkers in predicting early tumour recurrence (ETR) and survival in patients with resectable hepatocellular carcinoma (HCC). METHODS We examined the mRNA expressions of FGF19, FGFR4, klotho-beta (KLB), cyclin D1 (CCND1) and FGF4 in 151 surgically resected, primary unifocal HCCs through quantitative real-time polymerase chain reaction. Generalized additive models were fitted to detect nonlinear effects of continuous covariates and define thresholds of biomarker expressions. Univariate and multivariate analyses were performed to evaluate prognostic values of these biomarkers for tumour recurrence and patient survival. RESULTS Overexpression of FGF19, FGFR4, KLB, CCND1 and FGF4 mRNA was detected in 40%, 32%, 26%, 15% and 35% of 151 tumours respectively. ETR was the strongest prognostic factor predicting worse overall survival (hazard ratio [HR], 5.678; 95% confidence interval, 3.7-8.713; P

BackgroundThe incidence of breast cancer among younger East Asian women has been increasing rapidly over recent decades. This international collaborative study systemically compared the differences in age-specific incidences and pathological characteristics of breast cancer in East Asian women and women of predominantly European ancestry.MethodsWe excerpted analytic data from six national cancer registries (979 675 cases) and eight hospitals (18 008 cases) in East Asian countries and/or regions and, for comparisons, from the US Surveillance, Epidemiology, and End Results program database. Linear regression analyses of age-specific incidences of female breast cancer and logistic regression analyses of age-specific pathological characteristics of breast cancer were performed. All statistical tests were two-sided.ResultsUnlike female colorectal cancer, the age-specific incidences of breast cancer among East Asian women aged 59 years and younger increased disproportionally over recent decades relative to rates in US contemporaries. For years 2010–2014, the estimated age-specific probability of estrogen receptor positivity increased with age in American patients, whereas that of triple-negative breast cancer (TNBC) declined with age. No similar trends were evident in East Asian patients; their probability of estrogen receptor positivity at age 40–49 years was statistically significantly higher (odd ratio [OR] = 1.50, 95% confidence interval [CI] = 1.36 to 1.67, P < .001) and of TNBC was statistically significantly lower (OR = 0.79, 95% CI = 0.71 to 0.88, P < .001), whereas the probability of ER positivity at age 50–59 years was statistically significantly lower (OR = 0.88, 95% CI = 0.828 to 0.95, P < .001). Subgroup analyses of US Surveillance, Epidemiology, and End Results data showed similarly distinct patterns between East Asian American and white American patients.ConclusionsContrasting age-specific incidences and pathological characteristics of breast cancer between East Asian and American women, as well as between East Asian Americans and white Americans, suggests racial differences in the biology.

Objectives Peripheral blood parameters implicating the irreversible damages of cardiogenic shock under extracorporeal membrane oxygenation (ECMO) support patients were investigated. Methods The blood was collected from 23 cardiogenic shock cases at the time of ECMO installation, and 2, 6, 12, and 24h after oxygenation. Plasma levels of IL-2, IL-6, IL-7, IL-8, IL-10, IFN-γ, MCP-1, and carbonic anhydrase IX (CA IX) were determined by ELISA. Reactive oxygen species were measured by luminol and lucigenin and leukocyte subpopulations were analyzed by flow cytometry. Generalized additive models (GAMs) were performed to identify the death ranges of every variable and the variables were further discretized at each time point. The combination of predictors was selected from both original and discretized covariates by the generalized linear model (GLM) at each time point. Results Plasma IL-10 level was the most distinct biomarker between survivors and non-survivors after oxygenation. IL-10 sequentially partnered with IL-6, IL-7, and lymphocyte percentage at 2h, with CD3 + CD4 + T cells at 6h, with CA IX at 12h, and CD3 + T lymphocytes at 24h predicted death with AUCs 1.000, 0.975, 0.992, and 0.992, respectively. Conclusions Combination of the GAM plots and GLM models overcame the complexity of different disease categories. The systemic irreversible damages from cardiogenic shock ECMO cases might be detected from several peripheral blood parameters.

Background A standard measure to assess and predict violence is important for psychiatric services. No prospective study has examined the history of violence and heterogeneity of violence in predicting specific types of violence among inpatient with schizophrenia. Objectives This study aimed to prospectively examine the accuracy of prediction of types of violence using the Chinese modified version of Violence Scale (VS-CM) among inpatients with schizophrenia based on their past history of violence and the real occurrence of violence during hospitalization. Design A prospective cohort study design. Setting and participants A total of 107 adult patients with schizophrenia spectrum disorders, consecutively admitted to an acute psychiatric ward of a university hospital in Taiwan, were recruited. Method In addition to data about demographics and clinical illness, count records of the history of violence within one month prior to admission by interview and the actual occurrence of violence during the whole course of hospitalization by participant observation were collected using the VS-CM. Multivariate logistic analysis and area under the Receiver Operating Characteristic curve (AUC) analysis were applied to examine the predictive ability of the VS-CM. Results A patient's history of violence assessed by the VS-CM predicted the actual occurrence of violence during hospitalization with the Odds Ratio of 17.5 ( p =0.001). The predictive accuracy of the VS-CM had high sensitivity (97.0%), moderate positive predictive value (71.4%), and high negative predictive value (87.5%); however, the specificity was relatively low (35.0%). The AUC was 79.5% using the total scale of the VS-CM and 70.7–74.5% using the subscales in predicting corresponding types of violence. Conclusion The VS-CM is a valid and reliable measure of potential violence. It can be applied to assess and predict specific types of violence among inpatient with schizophrenia.

BackgroundThe effectiveness of education programs for pediatric patients receiving oral antibiotic suspension was unclear.MethodsWhen pediatric patients were prescribed antibiotics in powder form for suspension at the outpatient clinic of a university hospital, the responsible 150 caregivers were consecutively allocated into three education programs: Group 1 subjects read the package insert; Group 2 read a photograph-designed educational sheet; and Group 3 received a face-to-face medication education from a pharmacist with the photograph-designed educational sheet. The effectiveness of the three education programs for pediatric patients' caregivers was evaluated using a questionnaire comprised of 12 questions.ResultsThe proportions of the caregivers in Groups 1, 2 and 3 who answered the questionnaire perfectly with 100% accuracy were 2%, 14% and 74%, respectively (p

Objective To determine whether perfusion computed tomography (CT) is useful for identifying patients with poor-grade subarachnoid hemorrhage (SAH) with reversible etiologies and whether early obliteration in patients with poor-grade aneurysmal SAH leads to favorable outcomes. Methods Patients with new-onset aneurysmal SAH in World Federation of Neurological Surgeons (WFNS) grade IV or V neurologic condition who had perfusion CT performed at admission were eligible for the study. The study retrospectively enrolled 38 patients seen between January 2007 and July 2009. The decision to perform an early obliteration was made by the family after a discussion with the neurosurgeons, neurointensivists, and interventional radiologists. The functional outcomes were correlated with the Glasgow Outcome Scale (GOS) at 6 months, and quantitative perfusion CT data were collected. Results This study included 10 (26%) grade IV and 28 (74%) grade V patients. Favorable outcomes occurred in 19 (50%) patients, and 11 (29%) patients died. After a multivariate logistic regression analysis of the parameters, older age (odds ratio 1.104, P = 0.0317), bilateral prolonged mean transient time (MTT) at the thalami (odds ratio 4.155, P = 0.0362), and early obliteration (odds ratio 0.098, P = 0.003) were predictive of poor outcome. Conclusions Early bilateral prolonged MTT at the thalami and old age are associated with a poor outcome. Early obliteration benefits a significant portion of SAH patients.

In addition to diabetic retinopathy, diabetes also causes early retinal neurodegeneration and other eye problems, which cause various types of visual deficits. This study used a computer-based visual test (Macular Multi-Function Assessment (MMFA)) to assess contrast-dependent macular visual function in patients with type 2 diabetes to collect more visual information than possible with only the visual acuity test. Because the MMFA is a newly developed test, this study first compared the agreement and discriminative ability of the MMFA and the Early Treatment Diabetic Retinopathy Study (ETDRS) contrast acuity charts. Then symbol discrimination performances of diabetic patients and controls were evaluated at 4 contrast levels using the MMFA. Seventy-seven patients and 45 controls participated. The agreement between MMFA and ETDRS scores was examined by fitting three-level linear mixed-effect models to estimate the intraclass correlation coefficients (ICCs). The estimated areas under the receiver operating characteristic (ROC) curve were used to compare the discriminative ability of diseased versus non-diseased participants between the two tests. The MMFA scores of patients and controls were compared with multiple linear regression analysis after adjusting the effects of age, sex, hypertension and cataract. Results showed that the scores of the MMFA and ETDRS tests displayed high levels of agreement and acceptable and similar discriminative ability. The MMFA performance was correlated with the severity of diabetic retinopathy. Most of the MMFA scores differed significantly between the diabetic patients and controls. In the low contrast condition, the MMFA scores were significantly lower for 006Eon-DR patients than for controls. The potential utility of the MMFA as an easy screening tool for contrast-dependent visual function and for detecting early functional visual change in patients with type 2 diabetes is discussed.

Summary BackgroundandobjectivesRelativelylittleisknownaboutthelong-termoutcomesofdifferenthistologictypesof primary glomerulonephritis in Asian populations. Design, setting, participants, & measurements From 1993 to 2006, 987 patients undergoing renal biopsy were studied, and 580 patients (mean age=44.4 years, male=58.5%) with the four most common forms of glomerulonephritis (membranous nephropathy, focal and segmental glomerulosclerosis,IgA nephropathy, and minimal change disease) were selected for analysis. Median follow-up period was 5.9 (interquartile range=5.7) years. Results The focal and segmental glomerulosclerosis group displayed the highest incidence of ESRD (25.8%) and the fastest decline of estimated GFR (4.6 ml/min per 1.73 m 2 per year). The IgA nephropathy group also had a higher rate of ESRD than the membranous nephropathy patients (19.2% versus 4.3%, P,0.001). In contrast, the membranous nephropathy group exhibited an overall death rate similar to the focal and segmental glomerulosclerosis group (17.2% versus 14.4%) but higher than the IgA nephropathy and minimal change disease patients (4.6% and 3.7%, respectively, P,0.001). The most powerful predictor for ESRD was focal and segmental glomerulosclerosis, whereas the strongest predictor for all-cause mortality was membranous nephropathy with higher proteinuria. Protectors against ESRD included male sex and higher hemoglobin. Conclusions Most predictors for ESRD and overall mortality found in this ethnic Chinese cohort were similar to other studies. However, some risk factors linked with distinct glomerular pathologies displayed differential clinical outcomes. Clin J Am Soc Nephrol 7: ccc–ccc, 2012. doi: 10.2215/CJN.04500511

Summary Background The optimal dosage of intravenous proton pump inhibitors (PPIs) for the prevention of peptic ulcer rebleeding remains unclear. Aim To compare the rebleeding rate of high-dose and standard-dose PPI use after endoscopic haemostasis. Methods A total of 201 patients with bleeding ulcers undergoing endoscopic treatment with epinephrine injection and heater probe thermocoagulation were randomised to receive a high-dose regimen (80 mg bolus, followed by pantoprazole 8 mg/h infusion, n = 100) or a standard-dose regimen (pantoprazole 40 mg bolus daily, n = 101). After 72 h, all patients were given 40 mg pantoprazole daily orally for 27 days. Results There were no statistical differences in mean units of blood transfused, length of hospitalisation ≦5 days, surgical or radiological interventions and mortality within 30 days between two groups. Bleeding recurred within 30 days in six patients [6.2%, 95% confidence interval (CI) 1.3–11.1%] in the high-dose group, as compared to five patients (5.2%, 95% CI 0.6–9.7%) in the standard-dose group (P = 0.77). The stepwise Cox regression analysis showed end-stage renal disease, haematemesis, chronic obstructive pulmonary disease (hazard ratio: 37.15, 10.07, 9.12, 95% CI: 6.76–204.14, 2.07–49.01, 1.66–50.00 respectively) were independent risk factors for rebleeding and Helicobacter pylori infection was associated with lower risk of rebleeding (hazard ratio: 0.20, 95% CI: 0.04–0.94). Conclusions Following combined endoscopic haemostasis of bleeding ulcers, co-morbidities, haematemesis and H. pylori Status, but not PPI dosage, are associated with rebleeding (http://www.Clinical Trials.gov.ID: NCT00709046).

Background The standard of chemotherapy regimens for advanced or metastatic gastric cancer and the clinical outcome were heterogeneous in Asian versus non-Asian countries. This study aimed to explore predictors of safety and efficacy of chemotherapy for patients with advanced or metastatic gastric cancer.

Existing chronic kidney disease (CKD) is among the most potent predictors of postoperative acute kidney injury (AKI). Here we quantified this risk in a multicenter, observational study of 9425 patients who survived to hospital discharge after major surgery. CKD was defined as a baseline estimated glomerular filtration rate45 ml/min per 1.73 m(2). AKI was stratified according to the maximum simplified RIFLE classification at hospitalization and unresolved AKI defined as a persistent increase in serum creatinine of more than half above the baseline or the need for dialysis at discharge. A Cox proportional hazard model showed that patients with AKI-on-CKD during hospitalization had significantly worse long-term survival over a median follow-up of 4.8 years (hazard ratio, 1.7) [corrected] than patients with AKI but without CKD.The incidence of long-term dialysis was 22.4 and 0.17 per 100 person-years among patients with and without existing CKD, respectively. The adjusted hazard ratio for long-term dialysis in patients with AKI-on-CKD was 19.8 compared to patients who developed AKI without existing CKD. Furthermore, AKI-on-CKD but without kidney recovery at discharge had a worse outcome (hazard ratios of 4.6 and 213, respectively) for mortality and long-term dialysis as compared to patients without CKD or AKI. Thus, in a large cohort of postoperative patients who developed AKI, those with existing CKD were at higher risk for long-term mortality and dialysis after hospital discharge than those without. These outcomes were significantly worse in those with unresolved AKI at discharge.

Sorafenib plus metronomic tegafur/uracil therapy can induce tumor stabilization in advanced hepatocellular carcinoma (HCC) patients. This study evaluated the correlation of vascular response measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the clinical outcome.DCE-MRI was performed in advanced HCC patients treated with sorafenib (800 mg/d) plus tegafur/uracil (250 mg/m(2)/d based on tegafur) at baseline and after 14 days of treatment. An operator-defined region of interest was placed in the most strongly enhanced area of the tumor to measure the pharmacokinetic parameter K(trans). Changes in K(trans) after treatment were correlated with the best tumor response and survival.Thirty-one patients were evaluable. There were one partial response (PR), 18 stable disease (SD), and 12 progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Baseline K(trans) was higher in patients with PR or SD (median 1215.2 × 10(-3)/min, range 582.5-4555.3 × 10(-3)/min) than patients with PD (median 702.0 × 10(-3)/min, range 375.2-1938.0 × 10(-3)/min, p = 0.008). After 14 days of study treatment, the median K(trans) change was -47.1% (range -87.0 to -18.0%) in patients with PR or SD, and 9.6% (range -44.8 to +81%) in those with PD (p0.001). A vascular response, defined by a 40% or greater decrease in K(trans) after 14 days of study treatment, correlated with longer progression-free survival (median 29.1 vs. 8.7 weeks, p = 0.033) and overall survival (median 53.0 vs. 14.9 weeks, p = 0.016). Percentage of K(trans) change after treatment is an independent predictor of tumor response, progression-free survival, and overall survival.K(trans) measured by DCE-MRI correlated well with tumor response and survival in HCC patients who received sorafenib plus metronomic tegafur/uracil therapy.

Summary Background Pruritus is very common in uraemic patients, but the treatment remains challenging. Studies regarding narrowband ultraviolet B (NB-UVB) phototherapy for uraemic pruritus are rare. Objectives To investigate whether or not NB-UVB phototherapy is an effective treatment for uraemic pruritus. Methods We conducted a single-blind, randomized, controlled trial for patients with refractory uraemic pruritus. The treatment group received NB-UVB phototherapy three times per week for 6 weeks. The dose of NB-UVB started from 210 mJ cm−2 and was increased by 10% each time. The control group received time-matched exposures to long-wave UVA radiation. A visual analogue scale (VAS) score was evaluated weekly for pruritus intensity for 12 weeks. The characteristics of pruritus were also assessed by a questionnaire at baseline and after 6 weeks of phototherapy. Results Both the NB-UVB and control groups had significant and comparable improvement in the pruritus intensity VAS scores during the period of phototherapy and follow-up. Compared with the control group, the NB-UVB group showed a significant improvement in the involved body surface area affected by pruritus (P = 0·006), but not in sleep quality. More detailed regression and estimating analysis revealed that the patients in the NB-UVB group had lower pruritus intensity scores at week 6, week 10 and week 12. This may indicate a beneficial difference at certain time points, but the effect seems marginal. Conclusions NB-UVB phototherapy does not show a significant effect in reducing pruritus intensity compared with a control group for refractory uraemic pruritus. Further studies are warranted.

Kidney impairment is noted in primary aldosteronism (PA), and probably initiated by glomerular hyperfiltration.A prospectively defined survey was conducted on 602 patients who were suspected of PA in the multiple-center Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Estimated glomerular filtration rate (eGFR) was calculated and followed up at 1 yr after treatment.The diagnosis of PA was confirmed in 330 patients. Among them 17% of these patients had kidney impairment (eGFR60 ml/min/1.73 m²). Patients with PA had a higher prevalence of estimated hyperfiltration than those with essential hypertension (EH) (14.5% vs. 7.0%, p=0.005). The eGFR independently predicted PA (OR, 1.017) in the propensity-adjusted multivariate logistic model. In PA, plasma renin activity and lower serum potassium (p=0.018) was correlated with kidney impairment (p=0.001), while this relationship was not significant in patients with EH. Either unilateral adrenalectomy or treatment of spironolactone for PA patients caused a decrease of eGFR (p0.001). Pre-operative hypokalemia (p=0.013) and the long latency of hypertension (p=0.016) could enhance the significant decrease of eGFR after adrenalectomy.Patients with aldosteronism had relative estimated hyperfiltration than patients with EH. Calculation of eGFR may increase the specificity in identifying patients with PA. Our findings demonstrate the correlation of serum potassium and renin with estimated hyperfiltration in PA and their relationship to kidney damage. These results provide a high priority for future renal protective strategies and methods for the early diagnosis and prompt treatment of PA.

Background: Toxic epidermal necrolysis (TEN) is a rare life-threatening disorder characterized by extensive epidermal necrolysis. Its mortality which varies from 20% to 60% is related to risk factors such as age, extent of epidermal detachment, and base deficit. Objectives: The purpose of this study is to investigate the risk factors of mortality in our patients with TEN. Patients and methods: From the year 2000 to 2006, the patients with TEN admitted to the National Taiwan University Hospital Burn Center were studied retrospectively using chart review. Eleven potential risk factors including age, gender, underlying disease, malignancy, extent of epidermal detachment, tachycardia, serum urea, glucose, base deficit, leucopenia, and intravenous infusion of immunoglobulin (IVIG) were analyzed. Patients were grouped into survivors (n = 11) and nonsurvivors (n = 5) after intensive care treatment. Logistic regression was used in multivariate analysis for identifying important predictors of mortality. Results: The mean age of the patients with TEN was 58 years, while the mean total body surface area of epidermal necrolysis was 66.3%. The overall mortality rate was 31.3%. Among the potential risk factors, only serum bicarbonate

Objective To test the hypothesis that the presence of the PNPLA3 rs738409 G allele would increase the susceptibility of non-alcoholic fatty liver disease (NAFLD) in obese Taiwanese children. Study design A total of 520 obese children aged 6-18 years were recruited. Their PNPLA3 rs738409 genotypes—CC, CG, or GG—were detected by the 5'-nuclease assay. The effects of the PNPLA3 rs738409 G allele on pediatric NAFLD were evaluated based on liver ultrasonography findings and mean serum alanine aminotransferase levels in these children. Results NAFLD was present in 19.6% of the obese children. In comparison to the subjects with CC alleles, the risk of NAFLD was increased by 2.96-fold (95% CI, 1.57 to 5.59, P = .0008) in the subjects with CG alleles and by 5.84-fold (95% CI, 2.59 to 13.16; P .0001) in those with GG alleles. Variant PNPLA3 rs738409 genotypes were associated with increases in mean serum alanine aminotransferase level of 4.77 IU/L ( P = .0435) in subjects with CG alleles and of 10.86 IU/L ( P Conclusions The variant PNPLA3 rs738409 genotypes increased the risk of NAFLD in our population of obese Taiwanese children. The effect of the G allele on pediatric NAFLD followed a dominant genetic model.

Background: Epidermal growth factor receptor antagonists, such as gefitinib, erlotinib, and cetuximab, have been used in treating carcinomas. The efficacies have been proposed to correlate with skin reactions, but the most important predictive indicator is still unknown. Our aim was to investigate the types of skin toxicities and to analyze the major therapeutic predictive indicators in Taiwan. Methods: A retrospective analysis was used to study 68 patients with advanced non-small-cell lung cancer receiving gefitinib. Results: Acneiform eruption (41.2%), xerosis (38.2%), pruritus (26.5%), and paronychia (16.2%) composed most of the skin reactions. The univariate analysis revealed paronychia as the most substantial survival predictive indicator (p ¼0.0427). In the multivariate analysis, older patients with paronychia had better prognosis (p ¼0.0050). Women tended to develop paronychia (p ¼0.1098). Xerosis positively correlated with paronychia (p ¼0.0082). Conclusion: Paronychia is the most indicative survival predictive factor among the skin manifestations, and it correlates with age, gender, and xerosis. Elucidation of the relationship between cutaneous reactions can provide information on the epidermal growth factor receptor signaling mechanism of skin. Copyright 2011, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC. All rights reserved.

Background/Purpose Hypersensitivity reactions during oxaliplatin infusion are a major problem associated with its use. In this study, we investigated the characteristics and risk factors of these events. Methods All patients who had received oxaliplatin in outpatient settings from January 2006 to March 2007 in a medical center were enrolled in this retrospective study. All the oxaliplatin infusions were reviewed. Manifestations of hypersensitivity reactions and clinicopathological variables were collected from medical records. Results Three hundred and eighty-three patients with 3648 oxaliplatin infusions were reviewed. Forty-seven patients (12.7%) developed hypersensitivity reactions, which occurred after a median of 10 infusions. The median time of onset from start of infusion was 40 minutes. Most presentations (90.7%) were mild to moderate, but rechallenge with oxaliplatin led to a high chance of further reactions (71.4%). Cutaneous symptoms were the most prevalent manifestation, followed by respiratory symptoms. With each repeated infusion, the incidence of hypersensitivity reactions increased. Higher oxaliplatin dose per infusion was an independent risk factor for such reactions. Conclusion Patients treated with oxaliplatin for an extended period have a greater risk of oxaliplatin-related hypersensitivity reactions.

Background Taiwan has a remarkably high incidence of end-stage renal disease (ESRD). The objective of this study is to determine the association between prescribed herbal products containing aristolochic acid and ESRD. Study Design Population-based case-control study. Setting & Participants All new ESRD cases in Taiwan and a simple random sample (200,000 people) drawn from the national health insurance reimbursement database in 1997-2002. Predictor Age; sex; hypertension; diabetes; cumulative doses of nonsteroidal anti-inflammatory drugs, acetaminophen, and adulterated herbal supplements potentially containing aristolochic acid before the development of chronic kidney disease; and indications for prescribing such herbs, including chronic hepatitis, chronic urinary tract infection, chronic neuralgia, or chronic musculoskeletal diseases. Outcomes & Measurements Occurrence of ESRD through construction of multiple logistic regression models. Results There were 36,620 new ESRD cases from 1998 through 2002. After exclusion of cases with chronic kidney disease diagnosed before July 1, 1997, there were 25,843 new cases of ESRD and 184,851 controls in the final analysis. Women, older age, hypertension, and diabetes were significantly associated with increased risks of the development of ESRD. After adjustment for known risk factors, cumulative doses >60 g of Mu Tong (OR, 1.47 [95% CI, 1.01-2.14] for 61-100 g; OR, 5.82 [95% CI, 3.89-8.71] for >200 g) or Fangchi (OR, 1.60 [95% CI, 1.20-2.14] for 61-100 g; OR, 1.94 [95% CI, 1.29-2.92] for >200 g) were associated with increased risk of the development of ESRD with a dose-response relationship. This relationship persisted when analyses were limited to participants who consumed Limitations No measurement of renal function, no contact with patients, over-the-counter sales were not recorded, and potential underestimation of exposure dose for cases and ORs. Conclusions Consumption of >60 g of Mu Tong or Fangchi from herbal supplements was associated with an increased risk of developing kidney failure.

Background/Aims: Predicting models of operative morbidity and mortality in the geriatric population are important in the prevention of adverse surgical outcomes. Methods: A retrospective review of medical records was performed for patients over 80 years of age who underwent gastrointestinal surgery from 1998 to 2008. Results: 215 patients were identified with a mean age of 83.7 years. Overall morbidity and mortality rates were 48.8 and 14.4%, respectively. Multivariate logistic regression analysis revealed that serum albumin levels [odds ratio (OR) = 0.367, p = 0.0267], postoperative pneumonia (OR = 3.471, p = 0.0101), hollow organ perforation or anastomosis combined with leakage (OR = 7.600, p = 0.0126), and preoperative systemic inflammatory response syndrome (OR = 3.186, p = 0.0323) were significant predictors of hospital mortality. Moreover, albumin (OR = 0.270, p = 0.0002) and physical disability (OR = 3.802, p = 0.0009) were significant predictors of postoperative pneumonia, and albumin (OR = 0.491, p = 0.0212) and enterotomy (OR = 3.335, p = 0.0208) were significant predictors of surgical site infections. Conclusion: This study provides novel predicting models to identify the elderly surgical patients at high risk, who should receive more intensive preventive and perioperative care.

OBJECTIVE: Oxidative stress is increased in nonalcoholic fatty liver disease (NAFLD). Variants in the UGT1A1 gene contribute to increased bilirubin levels, and bilirubin can act as an antioxidant. We hypothesize that variant UGT1A1 genotypes reduce the risk for NAFLD development. METHODS: Two hundred thirty-four obese children 6 to 13 years of age were recruited. NAFLD was determined through liver ultrasonography. The UGT1A1 genotypes UGT1A1*6 and UGT1A1*28 were detected. We assessed the effects of UGT1A1 genotypes on pediatric NAFLD. RESULTS: In total, 12% of the obese children had NAFLD. The subjects with NAFLD had lower serum total bilirubin levels (0.25 ± 0.30 mg/dL) than did those without NAFLD (0.36 ± 0.38 mg/dL; P = .021). With conditioning on the effects of age- and gender-adjusted BMI, waist/hip ratio, and adiponectin levels, variant UGT1A1*6 genotypes were a protecting factor for NAFLD, with an estimated adjusted odds ratio of 0.31 (95% confidence interval: 0.11–0.91; P = .033), but variant UGT1A1*28 genotypes were not significantly associated with the occurrence of NAFLD. CONCLUSIONS: Variant UGT1A1*6 genotypes are associated with a lower risk of NAFLD in obese Taiwanese children. The UGT1A1 genotype is a new risk factor for pediatric NAFLD.

Late cardiovascular complications after intervention for coarctation of the aorta (CoA) might be common. Such data, especially in Asian populations, are still limited. A total of 169 patients with CoA who survived balloon (n = 41) or surgical (n = 128) intervention from 1986 to 2004 were enrolled. The total follow-up was 1,776 patient-years, and the patient age at last follow-up was 14.7 +/- 8.5 years. Reintervention for recoarctation, systemic hypertension, and left ventricular outflow tract obstruction (LVOTO) was subsequently noted in 57 (34%), 36 (21.3%), and 24 (14.2%) patients, respectively, without significant differences between the balloon and surgical groups. The 20-year freedom from reintervention, systemic hypertension, and LVOTO rate was 52%, 78.6%, and 80.8% in the balloon group and 59%, 51%, and 81.9% in the surgical group, respectively. The age at CoA intervention and the aortic geometry after CoA intervention of gothic type were common risk factors for reintervention for recoarctation and late systemic hypertension. In contrast, the presence of bicuspid aortic valves and gothic arch geometry after CoA intervention increased the risk of LVOTO. Plasma renin/aldosterone activities were not elevated in those with or without systemic hypertension. In conclusion, the profile of reintervention for recoarctation and late systemic hypertension after CoA interventions in our Asian cohort with CoA was similar to that observed in white patients. Asian patients might have a lower risk of LVOTO.

BACKGROUND The relationship between residual urine output and postoperative survival in maintenance hemodialysis patients is unknown. OBJECTIVE To explore the relationship between amount of urine before surgery and postoperative mortality and differences between postoperative nonanuria and anuria in maintenance hemodialysis patients. METHODS A total of 109 maintenance hemodialysis patients underwent major operations. Anuria was defined as urine output

Background Skin rash is the most common toxicity of epidermal growth factor receptor (EGFR)-targeted therapy. This study investigated the clinical and genetic factors associated with this skin rash. Methods Fifty-two non-small cell lung cancer patients enrolled in a clinical trial of first-line gefitinib treatment were genotyped for EGFR intron 1 CA repeat ([CA]n) polymorphism and single nucleotide polymorphisms at G-216T, C-191A, and R521K. The severity of skin rash was correlated with the genotypic and clinicopathological features. Results Seventeen patients (32.7%) developed grade 2–3 skin rashes within 4 weeks of treatment (early G2/3 rash). In the multivariate logistic regression analysis, only the [CA]n genotype was correlated with early G2/3 rash; and this relationship was modified by age. Early G2/3 rash developed in 21% of patients with homozygous long allele (19–22 repeats, L) genotype, 31% with heterozygous short allele (15–18 repeats, S)/L genotype, and 71% with S/S genotype, respectively. The estimated logarithm of odds ratio (ln OR) for early G2/3 rash, as compared to S/S genotype, for S/L genotype was −0.038 multiplied by age ( P = 0.011); and the ln OR for L/L genotype was −0.050 multiplied by age ( P = 0.004). Early G2/3 rash was correlated with tumor response in the multiple logistic regression analysis ( P = 0.027). However, the [CA]n genotype was not significantly correlated with tumor response ( P = 0.35). Conclusions EGFR [CA]n genotype appears to be a useful predictive marker of the development of skin rashes with gefitinib treatment.

Objectives This study aimed to compare the characteristics of psychiatric and nonpsychiatric suicidal inpatients in one general hospital and examine the predictors of completed suicide in the patients with suicidal acts during hospitalization. Methods One hundred ten study subjects were identified by the adverse event reports of suicidal acts during hospitalization from 1995 to 2004. Demographic data and clinical information were collected by chart reviews. Results Psychiatric inpatients with suicidal acts were mainly younger females with psychiatric diagnoses and previous suicide attempts. Nonpsychiatric suicidal inpatients had less suicide communication, performed suicidal acts more rapidly after admission and used more violent suicidal methods than the psychiatric inpatients did. Suicidal acts performed outside the hospital, use of violent suicidal methods and male gender increased the risk of suicide mortality in our suicidal inpatients. Conclusion This study suggests that suicide prevention efforts need to be tailored in psychiatric and nonpsychiatric wards according to differing patient risk characteristics in these patient cohorts.

Many patients with chordae tendineae rupture (CTR) of the mitral valve have obscure aetiologies. The association between pre-existing hypertension and idiopathic CTR was investigated.494 patients with CTR were identified by searching the computer database. For each patient with idiopathic CTR, three matched controls without CTR who were admitted to the same hospital for bone fractures were included.Among the 494 patients with CTR, 351 patients (71%) had idiopathic CTR, and 143 patients (29%) had secondary CTR. The prevalence of pre-existing hypertension was significantly higher in the idiopathic than in the secondary CTR group (50.9% vs 14.6%, p0.001). The odds ratio was 6.0 (95% CI 3.6 to 10.1). The percentage of patients without adequate blood pressure control was also higher in the idiopathic than in the secondary CTR group (23.1% vs 4.9%, p0.001). When compared with the fracture group, patients with idiopathic CTR also had a significantly higher prevalence of hypertension (50.9% vs 14.9%, p0.001), and the odds ratio was 5.9 (95% CI 4.5 to 7.8). After correction for age, the odds ratio of having hypertension was 3.6 (95% CI 2.1 to 6.3) and 6.6 (p0.001, 95% CI 5.0 to 8.8) when compared with the secondary CTR group and fracture group respectively.There is a strong association between pre-existing hypertension and idiopathic CTR. Whether or not this disease can be prevented by controlling hypertension deserves further investigation.

OBJECTIVE: To determine the risk of stroke associated with various antihypertensive drugs among previously uncomplicated hypertensive patients. METHODS: A retrospective cohort study was undertaken, covering the period from 1997 to 2004, of a 1,000,000-person random sample obtained from Taiwan's National Health Insurance reimbursement database. Between January 1999 and December 2004, 29 759 patients aged 30 years or older were identified as newly diagnosed uncomplicated hypertensive cases. They were followed up until the end of 2004. A time-dependent Cox's proportional hazards model was specified to analyze the risk of stroke development. RESULTS: From the 29,759 uncomplicated hypertensive patients, 1078 new cases of stroke were identified and followed up for at least 1 month during the study period, including 654 ischemic stroke cases. After adjustment for various risk factors, the hazard ratio of developing stroke was significantly higher for poor medication compliance (hazard ratio 1.5-1.9), old age, male sex, and comorbid diabetes mellitus and/or other heart diseases. Different categories of antihypertensive medications were not associated with differential effects on stroke development. In the subsequent analysis, we found that patients receiving pharmacotherapy with beta-blockers were 1.3 (95% confidence interval 1.0-1.6) times more likely to develop ischemic stroke than those who had been treated with other types of antihypertensive medication. CONCLUSION: Poor medication compliance is a key determinant of developing stroke among hypertensive patients. This study suggests that there has been no differential effect of antihypertensive medication on overall risk of stroke, whereas beta-blockers might be associated with more ischemic stroke. Further studies are needed to corroborate this hypothesis.

Objectives To examine the reliability and validity of a Chinese version of the Pediatric Evaluation of Disability Inventory in children with cerebral palsy. Design A prospective study. Subjects Two samples: 58 children with cerebral palsy (mean age 65.4 (standard deviation 29.9) months) and 89 normally developing children (mean age 43.5 (standard deviation 20.6) months). Methods The Pediatric Evaluation of Disability Inventory was translated and cross-culturally adapted into a Chinese version. The test-retest reliability, concurrent validity and discriminative validity were examined. Results Internal consistency was high (Cronbach's alpha: 0.90-0.99). Test-retest reliability was excellent (intraclass correlation coefficient: 0.982-0.998). The concurrent validity was good, as evidenced by the high correlation between the Pediatric Evaluation of Disability Inventory and the Functional Independence Measure for Children (Spearman's rho: 0.92-0.99). Logistic regression analysis demonstrated that the Pediatric Evaluation of Disability Inventory factor scores estimated by confirmatory factor analysis differentiated the children with cerebral palsy from normally developing children. Conclusion This study demonstrated that the Chinese version of the Pediatric Evaluation of Disability Inventory has good reliability and validity and provides support for its use in Chinese-speaking children with cerebral palsy.

Summary Background Epirubicin was effective for the treatment of non-small cell lung carcinoma (NSCLC). This study compared the efficacy and safety of gemcitabine plus conventional-dose epirubicin (GE) with gemcitabine–cisplatin (GC) as first-line chemotherapy for stage IIIB/IV NSCLC and evaluated the predictive value of nuclear expression of excision repair cross-complementing group 1 (ERCC1) and topoisomerase IIα (TopoIIα) on treatment outcome. Patients and methods Patients were randomized to GE (gemcitabine, 1000mg/m 2 on days 1, 8, and 15 and epirubicin, 70mg/m 2 on day 15) or GC (gemcitabine, 1000mg/m 2 on days 1, 8, and 15 and cisplatin, 80mg/m 2 on day 15). Treatment cycles were repeated every 4 weeks. Immunohistochemical study of ERCC1 and TopoIIα was done for patients with available tumor specimens. Results The response rate was 31.0% (95% CI 16.4–45.5%) for GC ( n =41) and 37.2.0% (95% CI 22.2–52.3%) for GE ( n =39). No significant differences in median time-to-treatment-failure (TTF) (GC, 6.1 months; GE, 6.2 months) or overall survival (GC, 13.2 months; GE, 21.5 months) were found between the two arms. Grade 3/4 neutropenia and febrile neutropenia were more common in GE. However, delay of protocol treatment due to leukopenia was similar between the two arms. Patients with expression of both ERCC1 and TopoIIα had a significantly shorter TTF (median 2.4 months, 95% CI 0.7–4.1 months) than other patients (median 8.8 months, 95% CI 5.8–11.8 months) ( p =0.04). Conclusion GE regimen is effective and well-tolerated for NSCLC patients. Expression of both ERCC1 and TopoIIα may be associated with poor response to chemotherapy.

Purpose: Abnormal spindle-like microcephaly associated (ASPM) plays an important role in neurogenesis and cell proliferation. This study is to elucidate its role in hepatocelllular carcinoma (HCC), particularly early tumor recurrence (ETR) and prognosis. Experimental Design: We used reverse transcription-PCR assays to measure the ASPM mRNA levels in 247 HCC and correlated with clinicopathologic and molecular features. Results: ASPM mRNA levels were high in fetal tissues but very low in most adult tissues. ASPM mRNA was overexpressed in 162 HCC (66%) but not in benign liver tumors. ASPM overexpression correlated with high α-fetoprotein (P = 1 × 10-8), high-grade (grade II-IV) HCC (P = 2 × 10-6), high-stage (stage IIIA-IV) HCC (P = 1 × 10-8), and importantly ETR (P = 1 × 10-8). ETR is the most critical unfavorable clinical prognostic factor. Among the various independent histopathologic (tumor size, tumor grade and tumor stage) and molecular factors (p53 mutation, high α-fetoprotein, and ASPM overexpression), tumor stage was the most crucial histologic factor (odds ratio, 14.7; 95% confidence interval, 6.65-33.0; P = 1 × 10-8), whereas ASPM overexpression (odds ratio, 6.49; P = 1 × 10-8) is the most important molecular factor associated with ETR. ASPM overexpression was associated with vascular invasion and ETR in both p53-mutated (all P values = 1 × 10-8) and non-p53-mutated HCC (P = 1 × 10-8 and 0.00088, respectively). Hence, patients with APSM-overexpressing HCC had lower 5-year survival (P = 0.000001) in both p53-mutated (P = 0.00008) and non-p53-mutated HCC (P = 0.0027). In low-stage (stage II) HCC, ASPM overexpression also correlated with higher ETR (P = 0.008). Conclusion: ASPM overexpression is a molecular marker predicting enhanced invasive/metastatic potential of HCC, higher risk of ETR regardless of p53 mutation status and tumor stage, and hence poor prognosis.

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an RNA-binding protein expressed in embryonic tissues and multiple cancers. To investigate the role of IMP3 in hepatocellular carcinoma (HCC), its protein expression in the surgically resected unifocal tumors of 377 HCC patients (296 men and 81 women) with ages ranging from 7 to 88 years (mean, 55.49 years) was analyzed by immunohistochemistry. IMP3 was expressed in 255 (67.6%) of 377 resected unifocal primary HCCs. IMP3 protein was predominantly expressed in tumor border and invasive front, and it was more abundant in the satellite nodules and tumor thrombi than in the main tumors. The expression correlated with high α-fetoprotein (>200 ng/mL, P 5 cm, P = 0.006), high tumor grade (P < 1 × 10−7), and high tumor stage with vascular invasion and various degrees of intrahepatic metastasis (P < 1 × 10−7). IMP3 expression predicted early tumor recurrence (P < 1 × 10−7) and was a strong indicator of poor prognosis (P < 0.0001). Depletion of IMP3 with RNA interference in HCC cell line HA22T caused a decrease in cell motility, invasion, and transendothelial migration. Microarray analysis revealed that IMP3 depletion was associated with downregulation of multiple genes involved in tumor invasion. Conclusion: Our results indicate that IMP3 plays an important role in tumor invasion and metastasis and is a strong prognostic factor for patients with HCC. (HEPATOLOGY 2008.)

Purpose To explore predictive factors for time to treatment failure (TTF) in chemotherapy-naive non–small-cell lung cancer (NSCLC) patients receiving gefitinib treatment. Patients and Methods We designed a phase II study to test gefitinib antitumor efficacy in advanced-stage, chemotherapy-naive NSCLC patients. Patients were treated with gefitinib 250 mg/d. Tumor assessments were performed every 2 months. Responding or stable patients were treated until progression or unacceptable toxicity. All scans were reviewed independently. EGFR exons 18-21 sequence, K-ras exon 2 sequence, and MET gene copy numbers were examined in available samples. Clinical or molecular predictors of TTF were examined by multivariate analysis. Results One hundred six patients were enrolled. Ninety patients had tumor samples for biomarker tests. Overall response rate was 50.9% (95% CI, 41.4% to 60.4%). Median TTF was 5.5 months, and median overall survival (OS) was 22.4 months. The response rate and median TTF of the patients with exon 19 deletion (n = 20) were 95.0% and 8.9 months, for exon 21 L858R mutation (n = 23) were 73.9% and 9.1 month, and for other types of EGFR mutations (N = 12) were 16.7% and 2.3 months, respectively. In multivariate analysis, the presence of EGFR deletion exon 19 or L858R EGFR mutations in adenocarcinoma patients predicted longer TTF. High copy number of MET seemed to correlate with shorter TTF in patients with gefitinib-sensitive activating EGFR mutations. Conclusion In this prospective study, EGFR exon 19 deletion or L858R mutations in adenocarcinoma were the best predictors for longer TTF in stage IIIB/IV chemotherapy-naive NSCLC patients receiving first-line gefitinib monotherapy.

The aim of the present study was to investigate whether imprint cytology can improve the diagnostic accuracy of computed tomography-guided transthoracic core biopsy. Between October 1997 and June 2004, thoracic lesions in 622 patients underwent biopsy using 19-gauge coaxial guiding needles and 20-gauge biopsy needles under computed tomography guidance. Touch imprint cytology and histopathology were performed for all biopsy specimens. Of these lesions, 431 (74.1%) were diagnosed as malignant, 151 (25.9%) as benign and 40 (6%) as nondiagnostic. Imprint cytology plus histology shows an improved diagnostic accuracy of 96.4% compared with that of imprint cytology alone (92.3%) or histopathology alone (93.0%). Procedure-related complications requiring further treatment occurred in eight (1.4%) patients. In conclusion, imprint cytology combined with histopathology can improve the diagnostic accuracy of computed tomography-guided transthoracic needle biopsy.

The aim of this study was to identify risk factors for redialysis in postoperative patients with acute renal failure (ARF) who had previously been weaned from acute dialysis. Although recovery of renal function is anticipated in patients with ARF, no data have been reported on successful weaning from acute dialysis.Retrospective observational case-control study in a 64-bed surgical ICU.Success in discontinuing dialysis was defined as cessation from dialysis for at least 30 days. A total of 304 postoperative patients who underwent acute renal replacement therapy in a surgical ICU between July 2002 and April 2005 were included. SOFA score biochemical data and renal function parameters were assessed on the day after the last session of renal replacement therapy, designated as day 0 (D0).We could wean 94 patients (30.9%) from acute dialysis for more than 5 days, and 64 of these (21.1%) were successfully weaned for at least 30days. The independent predictors for resuming dialysis within 30 days were: (a) longer duration of dialysis (OR 1.06), (b) higher SOFA score on D0 (OR 1.44), (c) oliguria (urine output100cc/8h; OR 4.17) on D1, and (d) age over 65 years (OR 6.35). The area under the ROC curve was 0.880. Two-way analysis of variance with repeated measurements over time showed a larger decline in SOFA score and an increase in urine output in patients with successful cessation of dialysis. Kaplan-Meier analysis showed a significant difference in early resumption of dialysis between patients with or without oliguria at D0.More than two-thirds of patients weaned from postoperative acute dialysis for more than 5 days were free of dialysis for at least 30 days. Less urine output, longer duration of dialysis, age over 65 years, and higher disease severity score are predictive of a patient's redialysis after initial weaning from acute dialysis.

Chinese are more sensitive to beta-blockers than Caucasians. However, data regarding beta-blocker therapy in heart failure (HF) patients in Taiwan are lacking. We aimed to evaluate the improvement of left ventricular function and the potential predictors of response to beta-blocker therapy in Taiwanese HF patients.We enrolled 34 HF patients with baseline left ventricular ejection fraction (LVEF)/= 40%. Beta-blockers were titrated up to the maximum tolerable dose. LVEF prior to beta-blocker usage and at the stable dose were obtained. We also sequenced the entire gene encoding beta1-adrenoceptor to assess the relationships between LVEF improvement and gene polymorphisms.Beta-blocker therapy (25 +/- 22 months) with a mean stable dose of 12 +/- 8 mg carvedilol/day significantly improved LVEF (from 28 +/- 8% to 40 +/- 15%, p0.001). Stepwise multiple linear regression analysis identified dilated cardiomyopathy (beta = 18.32, p = 0.0004), baseline LVEF (beta = -0.85, p = 0.0020), use of amiodarone (beta = -22.58, p = 0.0034) and square of digoxin dose (beta = -314.25, p = 0.0059) at stable beta-blocker dose as independent predictors of LVEF improvement, where beta is the estimated regression coefficient. We did not find any novel variant of beta1-adrenoceptor gene other than those previously reported at codons 49 and 389, with the allele distributions similar to those found in Caucasians, and these polymorphisms did not imply therapeutic response to beta-blocker.We demonstrated the therapeutic effects of beta-blockers in Taiwanese HF patients with a dose lower than what has been reported in Western people. Moreover, patients with the etiology of dilated cardiomyopathy or lower baseline LVEF predicted a greater LVEF improvement. The beta1-adrenoceptor gene polymorphisms were not responsible for the difference in sensitivity to beta-blockers in this Taiwanese population.